This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overriding goal of the proposed Transdisciplinary Imaging Genetics Center, an exploratory center, is to enhance our understanding of brain function in health and disease, through facilitation of development of a new discipline, referred to as imaging genetics. The Center does this by assembling an interdisciplinary team of experts from U.C. Irvine and the University of Toronto with experience in genomics, imaging analysis, statistical methods, and complementary areas viewed as key to this goal. These experts, complemented by the Center's consultants and External Advisory Board, have developed novel methods in their respective fields. The major focus of this project is to develop methods for combining imaging and genomics. It is clear that mental illness involves brain dysfunction that can be visualized with advanced brain imaging techniques. Mental illness as well as normal brain function also has a hereditary component;therefore, it is essential that the genes related to aspects of brain development, mental function and dysfunction, be considered. The integration of the imaging data with the rich genetic data resulting from the human genome project will enhance our understanding of brain function and mental illness. The value of this integration is illustrated in our initial studies that demonstrated an association between brain metabolism, clinical response and DRD1 alleles (Potkin at al, 2003), and between brain metabolism, risk of tardive dyskinesia, a motor side-effect on antipsychotic treatment, and DRD3 alleles (Potkin et al 2003b, Basile et al, 2002). The Center proposes the facilitation of an ongoing dialogue among the various fields involved by sponsoring annual international symposia and the development and implementation of a roadmap or work plan for this emerging discipline. The work plan for the Center will be guided by a transdiscipllnary collaboration between the Center investigators, their Steering Committee, the Center consultants, and the External Advisory Board. The Steering Committee and External Advisory Board are also charged with evaluating the Center's research progress and suggesting alternative solutions, as well as guiding the overall development of the Center. If the aims of the Center are achieved, the emerging field of genetic imaging will be positioned to enhance understanding of the biologically complex problem of mental illness, individual differences, and the interplay between genetics, environment, and brain function. Study of these fields individually has provided important revelations regarding brain dysfunction. Their integration and interaction, however, will provide new knowledge that would not be otherwise available. These goals could not be achieved without a unifying Center focused on a single integrative theme. The new knowledge generated by the Center holds considerable promise for improving diagnosis and treatment of mental illness.